Xu Jia-Li, Hu Ling-Min, Huang Ming-De, Zhao Wan, Yin Yong-Mei, Hu Zhi-Bin, Ma Hong-Xia, Shen Hong-Bing, Shu Yong-Qian
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Asian Pac J Cancer Prev. 2012;13(3):851-6. doi: 10.7314/apjcp.2012.13.3.851.
NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy.
Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS.
Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39).
Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.
NBS1在DNA双链断裂（DSB）修复中起关键作用。我们开展本研究以调查NBS1基因中两个关键多态性位点（rs1805794和rs13312840）对晚期非小细胞肺癌（NSCLC）患者铂类化疗疗效及预后的影响。
采用TaqMan方法对147例NSCLC患者的这两个多态性位点进行基因分型。使用逻辑回归分析计算优势比（OR）及其95%置信区间（CI），作为铂类化疗缓解率差异的衡量指标。采用Kaplan-Meier法和对数秩检验评估无进展生存期（PFS）和总生存期（OS）的差异。应用Cox比例风险模型评估PFS和OS的风险比（HR）。
这两个多态性位点均与铂类化疗的治疗反应无显著相关性。然而，携带rs1805794 CC变异基因型的患者与携带GG基因型的患者相比，PFS显著改善（16.0个月对8.0个月，P = 0.040）。多变量Cox回归分析进一步显示，rs1805974是PFS的显著有利预后因素[CC/CG对GG：调整后HR = 0.62，95%CI：0.39 - 0.99；CC对CG/GG：调整后HR = 0.56，95%CI：0.32 - 0.97]。同样，样本量较小的rs13312840也显示与PFS显著相关（CC对CT/TT：调整后HR = 25.62，95%CI：1.53 - 428.39）。
我们的研究结果表明，NBS1基因多态性可能是NSCLC预后的遗传生物标志物，尤其是在中国人群中接受铂类化疗时的PFS。
